My yields from the H3K4me3 positive control are low (i.e. below 5 ng), about the same as the IgG negative control. Did my experiment fail?
Similar yields from H3K4me3 and IgG controls do NOT imply CUT&RUN failure. H3K4me3 is a low abundance target, resulting in lower yields that are often similar to IgG. In these cases, use the total amount of CUT&RUN-enriched DNA for library prep. In EpiCypher's experience, good sequencing data with high signal-to-noise are still obtained.
If desired, a high abundance target (e.g. H3K27me3, EpiCypher 13-0055) can be used as an additional positive control, as yields will be much higher than IgG.